Ma. Barrett et al., STEREOSELECTIVE ABSORPTION AND HYDROLYSIS OF CEFUROXIME AXETIL DIASTEREOMERS USING THE CACO-2 CELL MONOLAYER MODEL, European journal of drug metabolism and pharmacokinetics, 22(4), 1997, pp. 409-413
Cefuroxime axetil, the orally active prodrug of cefuroxime is marketed
as a 1:1 mixture of two diastereomers designated as R (1'R, 6R, 7R) a
nd S (1'S, 6R, 7R). Prodrug hydrolysis is thought to occur during inte
stinal absorption, however little is known concerning the relative ava
ilability of cefuroxime from each isomeric form. The Caco-2 cell monol
ayer model was used to examine the possible stereoselectivity of absor
ption by measuring the accumulation and epithelial transport rate in t
he apical to basolateral direction of cefuroxime and cefuroxime axetil
following application of the mixture (1.0 mM) or individual diastereo
mers (0.5 mM) of cefuroxime axetil. Cefuroxime appearance in the basol
ateral chamber was in the order: mixture > R > S following application
of the prodrug. The accumulation of unchanged cefuroxime axetil was S
> R irrespective of the form applied, i.e. individual diastereomer or
the mixture. Such stereoselective differences in both absorption and/
or hydrolysis may contribute to the observed oral bioavailability (30-
50%) of cefuroxime in vivo.